Major Peter Strube CRNA MSNA APNP ARNP

Cell: 608-469-1750pstrube3000@yahoo.com

COX-2 Inhibitors, NSAIDS and Narcotic Review

We Must Start to Think Differently!

We can no longer sit by the wayside, we must make ourselves better.

Think outside the box…..

People don’t learn like we do?

What are the most abused Drugs?

Inhalant Abuse: Volatile substances that produce chemical vapors that can be inhaled to induce a psychoactive or mild altering effect. They act on the central nervous system except for nitrates. Not sure where, but it appears dopamine is the area that this works on in the brain.

Broad range of chemicals but the common characteristic is they are rarely if ever taken by any route but inhalation.

Volatile: Vapors at room tempAerosols: sprays that contain a propellant and solventGases: we use it all the time.Nitrates: Poppers or snappers. They relax smooth muscle and dilate blood vessels. They alter moods and are sexual enhancers.

Inhalant Abuse:Growing group of abused drugs…. Under 18 is the biggest group. Easy to get and easy to use. You can pick it up anywhere

Inhalants cause severe damage to the lungs, liver, kidneys, bone marrow and the brain. Can cause suffocation, stroke, loss of consciousness and death

Sniffing or snortingSprayingBaggingHuffingInhaling

Gasoline, glue, vegetable spray, hairspray, deodorant spray, paint thinner, transmission fluid, air freshener, Nitrites, Rush, Locker room popper, Whippets, Nitrous

Inhalant Abuse:Irregular and rapid heart rate; heart failureSudden sniffing death

Asphyxiation, suffocation, convulsions, seizures, chokingTrauma related to use

Pulmonary damage and inability to ventilate.Organ failureAggressive and violent behavior

Withdrawal Symptoms: Insomnia, irritability, cramps, nausea, tremors, depression, headache, confusion, convulsions

Keep up on Current Information:

Codeine----FDA alert…..

Keep a open mind…

HeroinOpioid analgesic synthesized from morphine.

Used to treat severe pain.

Inhalation (44-61%); Tran mucosal; IV (99%); Oral (<35%); Intranasal; Rectal, Vaginal; IM

Metabolism; HepaticHalf-life: <10 minutes90% renal as glucuronides rest biliary

Pain Control---Diamorphine, Diacetylmorphine

World Health Oganization Mild Pain…non-opioid +/- adjuvantModerate…phase 1 and weak opioidSevere…Phase 1 and 2 plus high narcotics, and blocks

Preemptive analgesia…Treat the pain before it occurs– Zofran Thoughts????

Surgical incision- inflammation at surgical site Peripheral sensitization wind-up central sensitization increase in the patients pain perception.

STEP 3STEP 2

andHigher doses of opioids

STEP 1Acetaminophen, NSAIDs, or COXIBs

andLocal/regional anesthesia

STEP 2STEP 1

andLow doses of opioids

11

Multimodal Approach to Acute Pain Management

Mild Pain

Moderate Pain

Severe Pain

Not our Friend, but we must embrace to make better

Multimodal analgesia combines two or more analgesic agents or techniques that act by different mechanisms to provide analgesia

ASA, WHO, ASPMN, and the Joint Commission recommend use of a multimodal approach

Opioid dose-sparing effects can be achieved via the use of non-opioid agents and regional blocks

ASA Task Force recommendations: – Unless contraindicated, all patients should receive an around-the-clock

regimen of a non-opioid agentNon-steroidal anti-inflammatory drugs (NSAIDs)Cyclooxygenase-2 specific drugs (COXIBs) Acetaminophen

– Consider supplemental regional anesthesia techniques

14

Multimodal Techniques for Perioperative Pain Management

Perioperative pain– Approximately 46 million inpatient procedures and 35 million

outpatient surgeries were performed in the US in 2006

– Despite new treatment standards, guidelines, and educational efforts, acute postoperative pain continues to be undertreated, with up to 75% of patients in the US still failing to receive adequate postoperative pain relief

– With the advent of Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, patients are now able to make decisions on hospitals based on quality of care, including quality of pain management

15

Acute Perioperative Pain

AcuteImmediate

Serves as a warning

Typically easier to treat

Typically has a end

Less than 6 months and subsides once the healing process is accomplished.

Chronic PainInvolves complex processes and pathology. Usually involves altered anatomy and neural pathways. It is constant and prolonged, lasting longer than 6 months and sometimes for life.

Last Longer than 3-6 months (most cite 6 months)

Serves NO purpose

Typically can not identify a cause

Leads to pain behaviors: Negative emotions, anxiety, depression, sleep deprivation, May lead to the patient seeking active end of life.

Very difficult to treat

ProstaglandinsAmong the most prevalent naturally occurring substances---

– Niacin Example:

Prostaglandins participate in autoregulation of renal blood flow and GFR and influence ion and water transport. NSAIDs have no adverse renal effects in healthy patients. But, when renal dysfunction presents, it is due to renal medullary ischemia.

Prostaglandins are important in protective mechanisms such as maintenance of the GI mucosal barrier, maintenance of renal perfusion, and platelet aggregation

Prostaglandins work as a messenger promoting the inflammatory response, resulting in expansion and rupture of blood vessels and progression of inflammation

Cyclooxygenase

A complex of enzymes necessary for the initial synthesis of prostaglandins, namely the conversion of arachadonic acid to endoperoxides

The search for better drugs led to the discovery of two different COX enzymes, COX 1 and COX 2

While the molecular arrangement of COX 1(two versions) and COX 2 are 70% identical, they are products of two different genes that reside on different chromosomes. COX 1 is a constitutive enzyme (present in all cells), while COX 2 has to be induced by “modulator” substances such as those appearing in the inflammatory response

The two COX enzymes attach to different sites on arachadonic acid. This important discovery allowed scientists to focus on ways to stop prostaglandin production by the less frequently present COX 2

Poor Pain Control Leads To…Decreased ability to ambulate:– Increased risk of thromboembolic phenomenon– Increased risk of PE

Splinting, atelectasis, and risk of pneumonia following abdominal and thoracic surgeries

Activation of neuroendocrine stress response to surgical pain stimulates the anterior pituitary– Release of stress hormones and catecholamines weight

loss, fatigue, immunosuppression, thromboembolism, hypercoagulability, dysrhythmias, urinary retention, and impaired pulmonary function

Summary:

One of the prostaglandins formed is PGE2:

Peripheral injury and inflammation increases local PGE2 synthesis

Surgical incision and resultant tissue damage results in release of prostaglandins including PGE2

Release begins at the moment of insult

Numerous studies suggest both central and peripheral sites of analgesic action for NSAIDsIncreased tissue PGE2 sensitizes afferent nerve endings

– Peripheral nociceptors – Lower firing threshold – Increased firing rate

Increases in tissue PGE2 levels are prevented by NSAIDs

NSAIDS

Analgesic Advantages Over Opioids:No respiratory depression/sedation Occasional CNS dysfunction including attention or memory deficits Elderly at increased risk Absence of tolerance or addiction potential Doesn’t reduce gastrointestinal motility

Postoperative Use in Acute Pain Can’t replace opioids in moderate to severe pain Insufficient analgesia when NSAID used as sole treatment of moderate to severe

pain Best considered as adjunct in multimodal therapy Neuraxial analgesia + NSAID IV PCA Opioid + NSAID Can be used to reduce opioid requirements (~25-40% sparing effect) and to reduce opioid related side effects Can be used alone as the pain subsides and in many outpatient procedures

Characteristics of NSAIDs and Side Effects

Positives: synergy with opioids, no impact on ventilation, long duration of action, less dosing variability

Negatives: inhibition of platelet aggregation, gastric ulceration (especially in the elderly and those on corticosteroids), renal dysfunction, bronchoconstriction in susceptible asthmatic patients by blocking prostaglandin E2 (this results in the pathway shifting toward lipooxygenase an ultimate production of inflammatory leukotrienes).

Lack of effects on platelet aggregation and bleeding is the primary advantage of COX 2 inhibitors vs nonselective NSAIDs

COX 2 inhibitors

The first of the selective COX 2 inhibitors, celecoxib (Celebrex) is approved by the FDA for the treatment of osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. Dose is 100-200 mg daily

A second COX 2 inhibitor, rofecoxib (Vioxx), was approved for the treatment of acute pain and for symptomatic treatment of osteoarthritis. In September 2004, it was removed from the market secondary to significant associated cardiovascular side effects such as acute MI and stroke

Valdecoxib is used for the above problems, but can be administered in a 40mg dose about 1 hour before surgery and another 40 mg can be given after surgery

Parecoxib is the only IV form of COX 2 inhibitor that is converted to Valdecoxib in vivo. Dosing is the same as Valdecoxib—US trials

Lack of effects on platelet aggregation and bleeding is the primary advantage of COX 2 inhibitors vs nonselective NSAIDs

Celebrex $1.25

Analgesic and anti-inflammatory agent.

Classified as a Cox-2

Action is in the periphery as well as the central nervous system

Stops pain at the site of transmission….noxious system.

200-400 mg

Contraindicated in renal insufficiency and a sulfa allergy

furosemide, fluconazole or ketoconazole, phenytoin, warfarin, aspirin

Aspirin (ASA, acetylsalicylic acid)The main mechanism of action of NSAIDs was clarified by Sir John Vane in 1971 who noted the inhibition of prostaglandin synthesis by aspirin

Irreversibly acetylates platelet COX 1. Lasts for the life of the platelet (8-12 days)

Absorption is hastened with lower gastric pH

Antipyretic, antiplatelet drug for prevention of MI and ischemic stroke

A relative contraindication for performing invasive surgical procedures is aspirin consumption within the last 8-12 days. BUT, withholding therapy can be deleterious, and most of the bleeding effects are gone by 2-3 days.

Two great works out about stents and continuing therapy.Eisenberg 2010Newscome 2008

Aspirin…….Pennies

Overdose can produce seizures—over 100 different combinations

Progression to respiratory and metabolic acidosis

Earliest sign of overdose is tinnitus

Acidosis favors the transport of salicylic acid from plasma to CNS, so sodium bicarbonate is often employed

Patients that have nasal polyps usually develop an aspirin-induced asthma (also with other NSAIDs like ketorolac) which can result in bronchospasm and hypotension

Acetaminophen $0.02/325mg

Not considered a ‘true’ NSAID because it lacks significant antiinflammatory effects

Useful analgesic and antipyretic useful for patients in whom salicylates are not recommended

No gastric irritation, platelet problems

Extensive hepatic metabolism

Hepatic necrosis and death may accompany a single dose of acetaminophen > 15 g. At doses > 4g, hepatotoxicity may occur (especially with ETOH use).

Remember that toxicity/necrosis occurs because of glutathione depletion.

Acetylcysteine increases glutathione stores and is most effective when given within 8 hours of ingestion

Part of more than 600 different drugs---knowyourdose.org

Acetaminophen

WOW!! is this one we really forgot aboutEven comes in a IV form; PARACETAMOL (2g/6hr)NOW AVAILABLE IN THE US>>> OFIRMEV-- CadenceVery limited side effects (hepatic in high doses)NO antiplatelet effectsNO gastric damage to the mucosa (high doses can get GI upset)NO effect on wound healing or bonesDoes not affect major organs in small doses

NO real reason why it works?? Mechanism of action is poorly understood --It may be working on a COX—3 route—really variant of COX - 1This is a safe weak to moderate analgesic that is quickly absorbed

Careful---JJ announcement!!!!Normal dose = 500 – 1000 mg for an adultPEDS (KISS) 10-20 mg/kg (tell parents when given)Give early (i.e. PO Tylenol with PO versed for a BMT) ? IV FORM NOWMAX DOSE::::::::: 4 gm a day adult

Careful with chronic alcoholism, liver dx, wasting chronicCan cause hepatotoxicity Avoid in G6-PD deficiency patients

This drug has a great effect with little if any side effects and should be considered a first line oral analgesic

Half life 1-4 hours; onset 30 minutes; 4-6 hours between dose

WOW did we forget about this one—USE THE IV FORM>>>>>>>>

OFIRMEV $10.00/1000mgIV acetaminophen injection: Cadence Pharm

Minimum dosing interval is every 4 hours

No change when going from IV to Oral

Administer over 15 min…..well….?????www.ofirmev.com

Do not exceed max daily doses.. Adult is 4 grams per dayPediatric is dosed at 15mg/kg with max of 75 mg/kg/day

CHEAPPPPPPPP

www.knowyourdose.org

OFIRMEVLiver issues is big

Contraindicated in patients with liver failure/hepatic injury or with known hypersensitivity to acetaminophen…

What about ETOH?

Common side effects are: N/V; HA: insomnia; constipation, pruritus and agitation and atelectasis

Using this drug may mask post surgical fever when used for post-operative pain.

Ketorolac $1.33/30mgVery effective analgesic, anti-inflammatory, and antipyretic actions

Available IM/IV doses are 15, 30 and 60 mg doses

30 mg of Ketorolac = 10 mg Morphine=100 mg Meperidine

After IM injection, peak plasma concentrations in 45-60 minutesHalf-life of about 6 hours

Not recommended for preop>inhibits platelet aggregation and may prolong bleeding time

Contraindications: bronchospasm, angioedema, nasal polyps, concurrent use of other NSAIDs, known allergy or intolerance to aspirin, history of GI bleeding, renal dysfunction, volume-depleted patients

Nice for certain surgeries, provided there are no contraindications as above: gynecologic surgery (D and C), inguinal hernia repair, breast surgery (biopsy)

Ketorolac (toradol)Until recently the only IV NSAID available for use in the USInhibits prostaglandin synthesis (COX)Prostaglandin synthesis which sensitizes and amplifies norciceptive inputThe use is limited by the dose ? Higher the dose the worse it is.Temporary effect on platelets (36 hours) inhibit thromboxane from A-2Renal issues (Kidney patients, hypovolemia, HTN)DiabetesElderly--Decrease the dose in elderly patients

There is a increased movement to just give if we deem appropriate and not ask the surgeons about it

Over 100 different combinations.

Issues

Peds = 0.5 mg/ kg (keep less than 15 mg)Smaller dose is better – remember this is a adjunctGI upsetInhibit platelet function and impaired coagulation – this is most like clinical insignificant in most patients in the correct doseIf you are worried of bleeding don’t do itOrtho has the strongest claim on not using is due to osteogenesis

Example: either a single one time dose OR NORMAL PATIENT (RARE) 15-30mg every 8 hours for no more than 5 days…. Do we need to do this ;; probably not; just a single doseRemember this can also be given IM and new Nasal route

Ibuprofen-Caldolor $10Think about Ketorolac.. Actions and side effects

Big differences… Less action on Cox 1 and more Cox 2 action..

What does this mean? Less bleeding.. More pain control can give anytime during the surgery… better now that we can give per--op

400mg/4ml or 800mg/8mlDilute and administer over 30 minutes400mg-800mg Over 30 min repeat every 6 hours PRN*

Fluids Fluids Fluids “ well hydrated prior to use”

Sprix-Nasal KetorolacShort Term use… Up to five days.

Some risk as IV or IM Ketorolac

Dose: 31.5mg or 15.75 mg each spray per nostril

Max daily dose is 63 mg

Opioids

Opium is the Greek word for juice or sap

An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the centeral and peripheral nervous system and the gastrointestinal tract. The receptors in these organ systems mediate both the beneficial effects and the side effects of opioids

Papaver somniferum

Opioid Anesthesia

Opioids remain the standard agent for acute pain management of moderate to severe pain

Opioids bind to opioid receptors in the CNS:

Inhibit transmission of the nociceptive input from the periphery to the spinal cord

Activate descending inhibitory pathways that modulate transmission in the spinal cord

Alter the limbic system

Nociceptive pain is generally more responsive to opioids than neuropathic pain

Opioid Anesthesia

Opioid side effects impede patient recovery: –Nausea, vomiting –Ileus, constipation –Itching –Sedation, mental clouding, confusion –Respiratory depression

Increased risk with co-adminstration of other sedative/hypnotics

Rest pain typically can be controlled with opioids alone

Pain with movement and PT/RT are typically not well controlled with single mode, opioid analgesia

Meperidine $1.14/50mgSide effects– orthostatic hypotension (more profound that with MS)– increased heart rate (atropine like effect)– delirium and seizures (normeperidine)– respiratory depression– mydriasis instead of miosis– dry mouth*** ACTIVE METABOLITE****

CV depression– 20 X greater than morphine due to direct myocardial depression– increased heart rate– decreased cardiac output – 60% bound to plasma proteins– elderly manifest decreased protein binding and increased plasma concentrations

Shivering: MeperidineMeperidine- unique among narcotics, decreases shivering by direct ?? hypothalamic effect. 12.5-50 mg IV will decrease shivering 50%– Anti-shivering, mostly kappa mediated?– Intravenous dose: 12.5-50 mg for shivering GO SMALL!!!

Synthetic opioid, mu receptor agonistHas some atropine like activity which may lead to tachycardia and dry mouth Possesses local effectsAvoid in patients on monoamine oxidase inhibitors: – May cause hyperpyrexia, convulsions, coma, hypertension, hypotension,

acidosis, death – Potential fatal drug interaction (serotonin-like syndrome)

Hydromorphone $0.89/1mgHydromorphone was first synthesized in Germany in 1924 Hydromorphone, a semi-synthetic μ-opioid agonist, is a hydrogenated ketone of morphine

Semisynthetic opioid – 4 to 6 times potency of morphine

0.015mg/kg dosing

Hydromorphone Water soluble opioid Compared to morphine: Slightly less water soluble Slightly faster onset Slightly shorter duration of action Associated with fewer adverse effects (pruritis, sedation, nausea, vomiting) Metabolite is Hydromorphone-3-Glucuronide (H3G) Neuroexcitatory properties Effects rare since H3G is produced in such small quantities

HydromorphoneMajor effects on the central nervous system and gastrointestinal tract.

These include analgesia, drowsiness, mental clouding, changes in mood, euphoria or dysphoria, respiratory depression, cough suppression, decreased gastrointestinal motility, nausea, vomiting, increased cerebrospinal fluid pressure, increased biliary pressure, pinpoint constriction of the pupils,

Increased parasympathetic activity and transient hyperglycemia.

Amazing For Epidural and Spinal Procedures: Epidural Dose: 10mcg/ml with localSpinal Dose: 0.002 milligram per kilogram

Sufentanil $3.52/50mcg

5 - 10X more potent than fentanylSufentanil 0.0035 mg = fentanyl 0.05 mg Safe therapeutic index: 25,211Dose: .025 - 30 µg/kgAnalgesic dose: 0.1 - 0.4 µg/kg IVMaintenance dose: 1µg/kg followed by 0.25-0.5 µg/kg/hr

High dose: 10 - 30 µg/kg

New PATCH coming out from Durrect Pharm….

Transdur-Sufentanil PatchEnding Phase 2 trials, so lets watch

this evolve

Remifentanil $68.34/2mg

Unique metabolism– Hydrolysis by non-specific esterases ---

The new “versed” has this mechanism

– Unaffected by age, gender, weight, hepatic or renal function

– Yet, the elderly are 2X as sensitive– Metabolite is renally excreted– Fast offset as it does not accumulate after long

administration (5 - 10 minutes)

Remifentanil

Because of fast offset and no accumulation, can be dosed to maximum effect

Fewer responses to intraoperative stress i.e. CEA

Higher dose of remifentanil results in 16% incidence of hypotension

Use of Remifentanil

Monitored Anesthesia Care (MAC)Dose: 25mcg/ml – 0.0125-0.15 mcg/kg/min– Single dose

1 µg/kg 90 seconds before local administrationdecreased to 0.5 µg/kg with Midazolam

– Infusion dose0.1 µg/kg/min 5 minutes before local↓ to 0.05 µg/kg/min after localwith midazolam, ↓ by 50%

REMIFOL

Use of RemifentanilNeurosurgery – minimal effect on ICP– modest effects on MAP

Post operative considerations– plan for analgesia must be in place prior to awakening

local infiltrationNSAIDslong acting narcotics given before emergence

General: 50 mcg/ml – 0.125-1.5 mcg/kg/min

Alfentanil $7.28--500mcg/ml

Used infrequently today1/5 - 1/10 as potent as FentanylAlfentanil 0.2mg = Fentanyl 0.05 mgSafe therapeutic index - 10801/3 duration of action of FentanylRapid onset– crosses blood/brain barrier easily

Brief duration of action due to redistribution

Retrobulbar blocks

What about? What in Common?

Ketamine $0.60/50 mgIF we get over the stigma from the past and understand how to truly dose this drug; it is one of the best anesthetic drugs around

Some early psych research suggests it helps with refractory depression form MOA withdrawal

Currently some research also suggests that until you get to very high doses there is no sympathetic response

The only true single anesthetic drug

Causes dissociative anesthesia; they only true anesthesia drug we have

NMDA receptor antagonistNMDA plays a important role in processing pain via glutamateReduces the need for opioidsMay reduce PONV??MH treatment = sequesters calcium

Ketamine the secret agentAnalgesia; 0.1-0.2 mg/kg IV At these low levels ; little if any side effects; (cardiovascular and psychological side effects)

At amnesia and analgesia doses; proper pretreatment with a benzo will help eliminate the psychological effects if any….

Keeping doses less than 1 mg/kg with a benzo is the max benefit of both drugs

Watch the eyes

KetamineKetamine and propofol mix for MAC casesTourniquet painIM Dart for patients: 4-8mg/kg – that is a lot (2-4mg/kg)

It is not a controlled substance at a lot of places and should be!Bronchodilator with asthmaNew concentrationsRaises ICP; raises IOP; Increases mental outcome of psych patientsCareful; some people are very prone to salivation; they may need a antimuscarinc agent

Post operative delirium is associated with females; greater than 15; doses greater than 2mg/kg; and history of nightmares (PTSD?)

Ketofol….ketamine PCA

THEORY OF KETOFOL:

PRO ARGUMENT:

Ketamine preserves respiratory function -> counterbalance the respiratory depression associated with propofol.

Ketofol reduces required amount of propofol -> less respiratory depression.

Less hypotensive episodes with ketofol versus propofol alone (ketamine preserves BP).

Ketofol leads to a reduction in opioid requirements.

Ketofol has fewer side effects (than ketamine)

CON ARGUMENT:Ketofol is nothing more than propofol sedation where fentanyl analgesia is replaced with dissociative ketamine.

Ketofol does not reduce respiratory depression or is a superior sedative as compared to either drug when used alone.

Remifol???

KETOFOL

Magnesium $0.54

This is a great electrolyte for pain control NMDA antagonistNeed to be careful on dosing

Hypermagnesemia can impair the release of acetylcholine and decrease motor end plate sensitivity of acetylcholine in the muscle

Keep levels low; keep dosing low; Magnesium has a very narrow therapeutic index;

Dose 1-2 grams in a normally healthy patient diluted in 50-100 ccs given over 30 minutes

It is easily excreted in the kidneys so those with renal failure will be prone to hyper levels

Blocks bradykinin release in the local vasculature; works great as a predosing agent in small doses for propofol -- dose this in mmols

Nitrous oxide (N²O)Combination of these gases that the patient inhales to help eliminate fear and to help the patient relax.

History– Dates back to 1844.– Dr. Horace Wells first used it on his patients

Effects– Non addictive.– Easy onset, minimal side effects, and rapid recovery.– Produces stage I anesthesia. – Dulls the perception of pain.

Nitrous OxideVery useful has NMDA receptor activity.

Rapid onset of analgesia and rapid recovery

In concentrations of 50% is as potent as 10mg of IM morphine.

Nitrous OxideHemodynamic StabilityIncreased RR; Decreased TVControversial studies in non human models on effects on DNA synthesisExpands Gas SpacesMay increase PONV

Most common still in Peds inductions

LMA’s and wake-ups

Methadone $1.00/10 MGSynthetic Opioid developed in Germany in 1937Not chemically related to morphine or heroinCheap and long actingTraditionally used with narcotic abuse Half life 24-36 hours -- fat solubleMu-receptor with limited action on NMDA 5 -10 mg single dose decreases the intra and post operative opioid requirements

This may be a great adjunct to both the chronic pain patient and the short term surgical patient.

Additionally this drug does not have the euphoric effects that other narcotics have and this may be of great benefit in those with addictive personalities.

Alpha-2

Alpha-2 Agonists:

Alpha-2 receptors play a role in modulating pain and alpha-2 agonists reduce pain

Clonidine and dexmedetomidine

Stimulate presynaptic alpha-2 receptors

Inhibit norepinephrine release from peripheral and central adrenergic nerves

Decreasing peripheral vascular resistance and heart rate

Alpha-2

Alpha-2 Agonists:

Clonidine and dexmedetomidine are also very good anxiolytics with minimal respiratory depression

Side effects include – Low blood pressure – Bradycardia – Dry mouth – Sedation

Alpha 2 adrenergic agonists -Clonidine

Alpha 2 receptors in the CNS (medullary vasomotor center) and spinal cord (substantia gelantinosa)

In the CNS, clonidine decreases SNS outflow via alpha 2 agonism

Sedation, decreased anesthetic requirements (via modification of K+ channels?) and analgesia are properties of clonidine

The sedative effects of clonidine are different from drugs that act on GABA receptors>>calm, easily aroused patient as opposed to a consciousness-clouded patient or a paradoxically agitated patient

150 – 400 mcg can be added neuraxially, producing dose-dependent analgesia, without the side effects of opioids

Neuraxial placement of clonidine inhibits substance P release

Alpha 2 adrenergic agonists -Clonidine

150 – 400 mcg can be added neuraxially, producing dose-dependent analgesia, without the side effects of opioids

Neuraxial placement of clonidine inhibits substance P release

Oral Clonidine 5mcg/kg prior to surgery decreases SNS response to laryngoscopy, decreases plasma catecholamine levels, decreases MAC requirements

Can be used as an adjunct in the management of acute ETOH withdrawl

Transdermal clonidine is effective for 7 days

LidocaineAmide local anesthetic; acting on sodium channels. Also works on dorsal horn neurons, muscarinic/dopaminergic/k/nicotinic and multiple other tissue receptors.

Reduces neural response to pain by blockade of inhibition of nerve conduction. This is achieved through suppression of conduction of myelinated A-delta and unmyelinated C nerve fibers.

Lidocaine is shown to suppress spinal cord sensitization, and inhibit spinal visceromotor neurons.

Lidocaine is an anti-inflammatory that improves outcomes related to post op pain.

Lidocaine InfusionsHalf-life 8 minutes90% hepatic metabolism P450-1A2—renal 10%Bolus 1-2.5 mg/kg LoadInfusion 1-3 mg/minStop infusion 60 minutes post skin closureOpioid Sparing effectImproved pain scores—some studies showed this effect for 48-72 hrsReturn to faster bowel functionDecreased length of stay

MexiletineOral Conger of Lidocaine: effective for neuropathic pain

Dose range 150-200 mg once or twice daily

Max dose is 1200 mg daily

Best range is 150-300mg TID

Diclofenac Patch 1%

Topical NSAIDSafe and effectiveCould lead to decreased systemic

aborbtion with a decrease risk of GI and Renal issues

12 hour patchMay have limits due to greasy texture

and smell

HerbalsCobra SprayFever FewSt Johns WortGlucosamineWhite willow barkBoswelliaDevils ClawBromelainCurcumin

FeverfewUsed to treat headaches, arthritis, as a fever reducer and pain reliever

Parthenolide in feverfew inhibits platelet aggregation

Used for treatment of migraines. With increased duration of use 3.5-8 years there is no difference in ADP or thrombin stimulated platelet aggregation. However serotonin induced platelet aggregation is decreased.

Some suggestions indicated it may help with chronic inflammation

This supplement/herbal interacts with antiplatelet and anticoagulants.

Links for Opioid Conversions –Please read!

http://cancer-research.umaryland.edu/CONVERT.htmhttp://www.eperc.mcw.edu/fastFact/ff_036.htmhttp://www.vhpharmsci.com/VHFormulary/Tools/Equianalgesic-dosing.htmwww.paincalc.info

Pain and Pain Management

This is a evolving field, this is only the tip of the iceberg. Keep learning.

Questions?

Thank you, Peter

–Dexamethasone

For Regional?? YES!

DexamethasoneSteroids are useful as adjuvant therapy for pain

Steroids can directly reduce pain in concert with opioid use and allow for a reduction in dose

Steroids reduce pain by inhibiting prostaglandin synthesis

Steroids have been shown to reduce spontaneous discharge in an injured nerve, which reduces neuropathic pain.